Fasting mimicking diet (FMD) as an immunoregulatory treatment for gastrointestinal autoimmune/inflammatory diseases

ABSTRACT

A method for treating autoimmune and/or inflammatory diseases includes a step of identifying a subject having a gastrointestinal autoimmune/inflammatory disease. A fasting mimicking diet (FMD) is administered to the subject for a first time period.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. provisional application Ser.No. 62/334,733 filed May 11, 2016, the disclosure of which is herebyincorporated in its entirety by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

The invention was made with Government support under Contract No.P01AG034906 awarded by the National Institutes of Health/NationalIntelligence Authority. The Government has certain rights to theinvention.

TECHNICAL FIELD

The present invention, in general, relates to methods for treating andreversing inflammatory bowel disease (IBD), which includes both Crohn'sdisease and ulcerative colitis, and other gastrointestinal autoimmuneand inflammatory diseases in part by reducing, preventing, or reversingimmune response of both innate and adaptive immunity and in part bypromoting intestinal regeneration.

BACKGROUND

Autoimmune diseases involve a miscommunication between innate andadaptive immunity and an imbalance between T lymphocytes populations,which play critical roles in the immuno-pathogenesis of manyautoimmune/chronic inflammatory diseases¹⁻³. It has been shown that bothhyperactive innate immune response (i.e. macrophages and dendriticcells), imbalance between autoreactive associated effector cells (i.e.CD4⁺ Th1 and CD4⁺ Th17) and anti-inflammatory associated regulatory Tcells (CD4⁺ Treg), and pro-inflammatory cytokine productions contributeto the pathogenesis of major gastrointestinal autoimmune/inflammatorydiseases including Crohn's disease (CD), ulcerative colitis (UC),irritable bowel syndrome, celiac disease, microscopic colitis(collagenous and lymphocytic colitis), and Bejcet disease³⁻⁸. See alsoTable 1 for comprehensive list of autoimmune/inflammatorydiseases^(5,8-11).

Current therapies for gastrointestinal autoimmune/inflammatory diseasesare monoclonal antibodies or a combination therapy with monoclonalantibody and immunomodulatory treatment; however the efficacy of themonoclonal or the combination therapy are still controversial and itslong-term safety still remains to be investigated¹²⁻¹⁴. Moreover, thelimitation in the number of efficacious monoclonal antibodies, infusionreactions, immunogenicity, high-cost, and adverse events such aslymphoma or acute anaphylaxis limit their applications^(15,16).

Accordingly, there is a need for improved methods of treating autoimmuneand/or inflammatory disease, and in particular for treatinggastrointestinal autoimmune/inflammatory disease.

SUMMARY

The present invention solves one or more problems of the prior art byproviding a method for treating autoimmune and/or inflammatory disease.The method includes a step of administering a fasting mimicking diet(FMD) to the subject for a first time period to a subject having agastrointestinal autoimmune and/or inflammatory disease.

In another embodiment, a diet package for practicing the methods setforth herein is provided. The diet package includes a first set ofrations for a first diet to be administered for a predetermined timeperiod to a subject with administration schedule. The first dietproviding less than 40 grams of sugar for day 1; less than 30 grams ofsugar for days 2 to 5 and any remaining days; less than 28 grams ofprotein for day 1; less than 18 grams of protein for days 2 to 5 and anyremaining days; 20-100 grams of monounsaturated fats for day 1; 6-30grams of polyunsaturated fats for day 1; 2-12 grams of saturated fatsfor day 1; 10-50 grams of monounsaturated fats for days 2 to 5 and anyremaining days; 3-15 grams of polyunsaturated fats for days 2 to 5 andany remaining days; 1-12 grams of saturated fats for days 2 to 5, or anyremaining days; a micronutrient composition on each day and anyremaining days; and optionally instructions for administering the dietpackage to a subject for treating autoimmune and/or inflammatorydisease. Characteristically, the instructions including theadministration schedule.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 . FMD reduced intestinal inflammation/colitis severity validatedby Hemoccult test: The FMD treatment reduced fecal bleeding compare tothe control diet treatment (Blue staining indicates a presence of fecalblood).

FIG. 2 . FMD increases endogenous corticosterone production.Corticosterone is a glucocorticoid hormone with broad anti-inflammatoryand immunosuppressive effects affecting leukocyte distribution,trafficking, and death¹⁷⁻²⁰ The FMD treatment resulted in an increasecorticosterone level compared to the control diet treatment.

FIG. 3 . Table 1: FMD-altered both innate and adaptive immune responseand cytokines as therapeutic targets for treating major gastrointestinalautoimmune/inflammatory diseases.

FIG. 4 . Table 2: FMD prevented colon shortening. Shortening of thecolon is classically associated with DSS induced colitis. The FMDtreated group showed protection against the DSS-induced colon shorteningcompared to the control diet treated group (p<0.01).

FIG. 5 . Table 3: FMD causes colon regeneration. Shortening of the colonis classically associated with DSS induced colitis. The FMD cyclesapplied after the colon was shortened by the IBD, caused a majorincrease in the colon length, indicating a strong regenerative effect(p<0.01).

FIG. 6 . Table 4. FMD reduces innate immune response. The FMD reducedthe number of dendritic cells and macrophages of innate immune systemcompared to the control.

FIG. 7 . Table 5: FMD reduces adaptive immune response. The FMD groupreduced the number of B lymphocytes and autoimmune associated Th1 andTh17 lymphocytes compared to the control diet group while it increasedthe anti-inflammatory regulatory T cells (Treg).

FIG. 8 . Table 6: FMD reduces autoimmune-associated cytokinesproductions (IFN-γ and IL-17) and increases an anti-inflammatorycytokine production (IL-10).

DETAILED DESCRIPTION

Reference will now be made in detail to presently preferredcompositions, embodiments, and methods of the present invention whichconstitute the best modes of practicing the invention presently known tothe inventors. The Figures are not necessarily to scale. However, it isto be understood that the disclosed embodiments are merely exemplary ofthe invention that may be embodied in various and alternative forms.Therefore, specific details disclosed herein are not to be interpretedas limiting, but merely as a representative basis for any aspect of theinvention and/or as a representative basis for teaching one skilled inthe art to variously employ the present invention.

Except in the examples, or where otherwise expressly indicated, allnumerical quantities in this description indicating amounts of materialor conditions of reaction and/or use are to be understood as modified bythe word “about” in describing the broadest scope of the invention.Practice within the numerical limits stated is generally preferred.Also, unless expressly stated to the contrary: percent, “parts of,” andratio values are by weight; the description of a group or class ofmaterials as suitable or preferred for a given purpose in connectionwith the invention implies that mixtures of any two or more of themembers of the group or class are equally suitable or preferred;description of constituents in chemical terms refers to the constituentsat the time of addition to any combination specified in the description,and does not necessarily preclude chemical interactions among theconstituents of a mixture once mixed; the first definition of an acronymor other abbreviation applies to all subsequent uses herein of the sameabbreviation and applies mutatis mutandis to normal grammaticalvariations of the initially defined abbreviation; and, unless expresslystated to the contrary, measurement of a property is determined by thesame technique as previously or later referenced for the same property.

The term “comprising” is synonymous with “including,” “having,”“containing,” or “characterized by.” These terms are inclusive andopen-ended and do not exclude additional, unrecited elements or methodsteps.

The phrase “consisting of” excludes any element, step, or ingredient notspecified in the claim. When this phrase appears in a clause of the bodyof a claim, rather than immediately following the preamble, it limitsonly the element set forth in that clause; other elements are notexcluded from the claim as a whole.

The phrase “consisting essentially of” limits the scope of a claim tothe specified materials or steps, plus those that do not materiallyaffect the basic and novel characteristic(s) of the claimed subjectmatter.

It is also to be understood that this invention is not limited to thespecific embodiments and methods described below, as specific componentsand/or conditions may, of course, vary. Furthermore, the terminologyused herein is used only for the purpose of describing particularembodiments of the present invention and is not intended to be limitingin any way.

It must also be noted that, as used in the specification and theappended claims, the singular form “a,” “an,” and “the” comprise pluralreferents unless the context clearly indicates otherwise. For example,reference to a component in the singular is intended to comprise aplurality of components.

Throughout this application, where publications are referenced, thedisclosures of these publications in their entireties are herebyincorporated by reference into this application to more fully describethe state of the art to which this invention pertains.

Throughout this application, where publications are referenced, thedisclosures of these publications in their entireties are herebyincorporated by reference into this application to more fully describethe state of the art to which this invention pertains.

The terms “kilocalorie” (kcal) and “Calorie” refer to the food calorie.The term “calorie” refers to the so-called small calorie.

The term “fasting mimicking diet” (FMD) means a diet that mimics theeffects of fasting typically by providing a subject with at most 50% oftheir normal caloric intake but with some nutritional component so thatfasting is mimicked while a subject is not completely starved. Examplesof useful fasting mimicking and enhancing diets and method formonitoring the effects of these diets on markers such as IGF-1 andIGFBP1 in the context of the present invention are set forth in U.S.patent application Ser. No. 14/273,946 filed May 9, 2014; Ser. No.14/497,752 filed Sep. 26, 2014; Ser. No. 12/910,508 filed Oct. 22, 2010;Ser. No. 13/643,673 filed Oct. 26, 2012; Ser. No. 13/982,307 filed Jul.29, 2013; Ser. No. 14/060,494 filed Oct. 22, 2013; Ser. No. 14/178,953filed Feb. 12, 2014; Ser. No. 14/320,996 filed Jul. 1, 2014; Ser. No.14/671,622 filed Mar. 27, 2015; the entire disclosure of these patentapplications is hereby incorporated by reference. The fasting mimickingdiet set forth in U.S. patent application Ser. Nos. 14/060,494 and14/178,953 are found to be particularly useful in the present invention.Additional examples of FMD diets are found in U.S. patent applicationSer. No. 15/148,251 and WIPO Pub. No. WO2011/050302 and WIPO Pub. No.WO2011/050302; the entire disclosures of which are hereby incorporatedby reference.

The present invention solves one or more problems of the prior art byproviding in at least on embodiment, a method for treating autoimmuneand/or inflammatory disease. The method includes a step of includes astep of identifying a subject having a gastrointestinalautoimmune/inflammatory disease. A fasting mimicking diet (FMD) isadministered to the subject for a first time period. Typically, theadministration of the FMD is repeated a plurality of times atpredetermined intervals. In a refinement, the FMD is repeated atintervals from one week to 6 months. In some variations, a normal dietis administered between cycles of the FMD. In this context, a normaldiet is a diet of sufficient caloric intake to maintain the subject'sweight. In a refinement, the normal caloric intake provides the subjectwith 1500 to 2500 kcal or 1800 to 2300 kcal, or 1800 to 2000 kcal.

The FMD is administered to the subject for a first time period. In somevariations, the first time period is equal to or greater than, inincreasing order of preference, 3, 5, 6, or 7 days. In addition, thefirst time period is equal to or less than, in increasing order ofpreference, 20, 15, 10, or 8 days. In a refinement, the first timeperiod 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In another refinement, thefirst time period is 5 to 10 days. In some variations of the methods setforth herein, the fasting mimicking and enhancing diet is repeated atfirst intervals. For example, the fasting mimicking and enhancing dietcan be initiated once a month for the duration of the subject'streatment which can be 3 months to a year or more (e.g., 1 to 5 years).

In some variations, the fasting mimicking diet for each of the methodsset forth herein provides at most, in increasing order of preference,50%, 40%, 30%, or 100% of the subject's normal caloric intake. In arefinement, the fasting mimicking diet provides at least, in increasingorder of preference, 5%, 10%, or 20% of the subject's normal caloricintake. The subject's normal caloric intake is the number of kcal thatthe subject consumes to maintain his/her weight. The subject's normalcaloric intake may be estimated by interviewing the subject or byconsideration of a subject's weight. As a rough guide, subject's normalcaloric intake is on average 2600 kcal/day for men and 1850 kcal/day forwomen. In certain instances, the fasting mimicking diet provides thesubject with from 700 to 1200 kcal/day. In a particularly usefulrefinement, the fasting mimicking diet provides a male subject ofaverage weight with at most 1100 kcal/day and a female subject ofaverage weight with at most 900 kcal/day. In some refinements, thefasting mimicking diet provides at most, in increasing order ofpreference, 1500 kcal/day, 1400 kcal/day, 1300 kcal/day, 1200 kcal/day,1100 kcal/day, 1000 kcal/day, 900 kcal/day, 800 kcal/day, 700 kcal/day,600 kcal/day, 500 kcal/day, or 2500 kcal/day. In some furtherrefinements, the fasting mimicking diet provides at least, in increasingorder of preference, 0 kcal/day, 10 kcal/day, 100 kcal/day, 200kcal/day, 300 kcal/day, 400 kcal/day, or 500 kcal/day.

In certain variations, the fasting mimicking and enhancing diet providesfrom 4.5 to 7 kilocalories per pound of subject for a first day (day 1)and then 3 to 5 kilocalories per pound of subject per day for the secondto the final day. After a cycle of the fasting mimicking and enhancingdiet, a second diet is administered to the subject for a second timeperiod. In a refinement, the second diet provides an overall calorieconsumption that is within 20 percent of a subject's normal calorieconsumption for 10 to 26 days (e.g., immediately) following the fastingmimicking and enhancing diet.

The consumption guidelines for the FMD include Nutrition Facts relativeto calories, macronutrients and micronutrients. Calories are consumedaccording to the user's body weight. Total calorie consumption is 4.5-7calorie per pound (or 10-16 calorie per kilogram) for day 1 and 3-5calorie per pound (or 7-11 calorie per kilogram) for day 2 to 5 and anyremaining days. In a variation of the embodiments set forth above, thefasting mimicking diet provides less than 40 grams of sugar for day 1,less than 30 grams of sugar for days 2 to 5 and any remaining days, lessthan 28 grams of protein for day 1, less than 18 grams of protein fordays 2 to 5 and any remaining days, 20-100 or 20-30 grams ofmonounsaturated fats or more to reach a higher calorie consumption(i.e., to reach a higher predetermined calorie consumption) for day 1,6-30 or 6-10 grams of polyunsaturated fats or more to reach a highercalorie consumption for day 1, 2-12 grams of saturated fats or more toreach a higher calorie consumption for day 1, 10-50 or 10-15 grams ofmonounsaturated fats or more to reach a higher calorie consumption fordays 2 to 5 and any remaining days, 3-15 or 3-5 grams of polyunsaturatedfats or more to reach a higher calorie consumption for days 2 to 5 andany remaining days, 1-12 or 1-6 grams of saturated fats or more to reacha higher calorie consumption for days 2 to 5, or any remaining days, anda micronutrient composition on each day and any remaining days. To reachthe higher calorie consumption described earlier which can be as high asa normal calorie intake, equal parts of the fats described above and ofvegetable derived carbohydrate sources (vegetable soups and chips)described elsewhere in the patent can be used. A FMD with caloriesranging from 50% restricted to normal, is expected to be effective butless effective than the 50% or more restricted diet described in thisapplication.

In another variation of the embodiments set forth above, the fastingmimicking diet provides 8-10 kcal per kilogram body weight for each dietday. In this variation, the fasting mimicking diet provides less than 30grams of sugar for each diet day, less than 18 grams of protein for eachdiet day, 9-15 grams of monounsaturated fats for each diet day, and2.5-4.5 grams of polyunsaturated fats for each diet day and 1-5.5 gramsof saturated fats for each diet day.

In still another variation of the embodiments set forth above, thefasting mimicking diet provides 5-8 kcal per kilogram body weight foreach diet day. In this variation, the fasting mimicking diet providesless than 20 grams of sugar for each diet day, less than 12 grams ofprotein for each diet day, and 6.5-10 grams of monounsaturated fats foreach diet day, 2.5-4.5 grams of polyunsaturated fats for each diet dayand 1.5-4 grams of saturated fats for each diet day.

In still another variation of the embodiments set forth above, thefasting mimicking diet provides 0-3 kcal per kilogram body weight foreach diet day. In this variation, the fasting mimicking diet providesless than 5 grams of sugar for each diet day, less than 3 grams ofprotein for each diet day, and less than 2.5 grams of monounsaturatedfats for each diet day, less than 1 grams of polyunsaturated fats foreach diet day and less than 1 grams of saturated fats for each diet day.

The fast mimicking diet can include virtually any source of fat, butsources high in unsaturated fat, including monounsaturated andpolyunsaturated fat sources, are particularly useful. Suitable examplesof monounsaturated food sources include, but are not limited to, peanutbutter, olives, nuts (e.g., almonds, pecans, walnut, pistachios,cashews, macadamia), avocado, seeds (e.g., sesame), oils (e.g., olive,sesame, peanut, canola), etc. Suitable examples of polyunsaturated foodsources include, but are not limited to, walnuts, seeds (e.g., pumpkin,sunflower), flaxseed, fish (e.g., salmon, tuna, mackerel), oils (e.g.,safflower, soybean, corn). The first diet also includes a componentselected from the group consisting of vegetable extracts, minerals,omega-3/6 essential fatty acids, and combinations thereof. In onerefinement, such a vegetable extract provides the equivalent of 5recommended daily servings of vegetables. Suitable sources for thevegetable extract include, but are not limited to, bokchoy, kale,lettuce, asparagus, carrot, butternut squash, alfalfa, green peas,tomato, cabbage, cauliflower, beets. Suitable sources for the omega-3/6essential fatty acids include fish such as salmon, tuna, mackerel,bluefish, swordfish, and the like.

In a variation, the fasting mimicking diet includes the followingmicronutrients (at least 95% non-animal based): over 5,000 IU of vitaminA per day (day 1 to the final day); 60-240 mg of vitamin C per day (day1 to the final day); 400-800 mg of Calcium per day (day 1 to the finalday); 7.2-14.4 mg of Iron per day (day 1 to the final day); 200-400 mgof Magnesium per day (day 1 to the final day); 1-2 mg of copper per day(day 1 to the final day); 1-2 mg of Manganese per day (day 1 to thefinal day); 3.5-7 mcg of Selenium per day (day 1 to the final day); 2-4mg of Vitamin B1 per day (day 1 to the final day); 2-4 mg of Vitamin B2per day (day 1 to the final day); 20-30 mg of Vitamin B3 per day (day 1to the final day); 1-1.5 mg of Vitamin B5 per day (day 1 to the finalday); 2-4 mg of Vitamin B6 per day (day 1 to the final day); 240-480 mcgof Vitamin B9 per day (day 1 to the final day); 600-1000 IU of Vitamin Dper day (day 1 to the final day); 14-30 mg of Vitamin E per day (day 1to the final day); over 80 mcg of Vitamin K per day (day 1 to the finalday); 16-25 mcg Vitamin B12 are provided during the entire 5-day period;600 mg of Docosahexaenoic acid (DHA, algae-derived) are provided duringthe entire 5-day period. The FMED diet provides high micronutrientcontent mostly (i.e., greater than 50 percent by weight) from naturalsources including: Kale, Cashews, Yellow Bell Pepper, Onion, LemonJuice, Yeast, and Turmeric. Mushroom, Carrot, Olive Oil, Beet Juice,Spinach, Tomato, Collard, Nettle, Thyme, Salt, Pepper, Vitamin B12(Cyanocobalamin), Beets, Butternut Squash, Collard, Tomato, Oregano,Tomato Juice, Orange Juice, Celery, Romaine Lettuce, Spinach, Cumin,Orange Rind, Citric Acid, Nutmeg, Cloves, and combinations thereof.Table 1 provides an example of additional micronutrient supplementationthat can be provided in the FMD diet:

In some variations, a second diet is administered to the subject for asecond time period. The second diet provides an overall calorieconsumption that is within 10 percent of a subject's normal calorieconsumption. Although the present invention is not significantly limitedby the second time period, the second time period can be from 7 days to6 months or longer. Typically, the second diet can be administered for25 to 26 days or longer following the fasting mimicking and enhancingdiet. In some refinements, the second diet provides at most, inincreasing order of preference, 2500 kcal/day, 2400 kcal/day, 2300kcal/day, 2200 kcal/day, 2100 kcal/day, 2000 kcal/day, 1900 kcal/day,1800 kcal/day, 1700 kcal/day, 1600 kcal/day, or 1500 kcal/day. In somefurther refinements, the second diet provides at least, in increasingorder of preference, 1200 kcal/day, 1300 kcal/day, 1400 kcal/day, 1500kcal/day, 1600 kcal/day, 1700 kcal/day, or 1800 kcal/day.

In another embodiment, a diet package for treating autoimmune and/orinflammatory disease is provided. In a variation, the diet includes thecaloric, food and nutritional specification set forth above inaccordance to the methods and administration schedule set forth above.For example, the diet package includes a first set of rations for afirst diet to be administered for a predetermined time period to asubject with administration schedule. The first diet providing less than40 grams of sugar for day 1; less than 30 grams of sugar for days 2 to 5and any remaining days; less than 28 grams of protein for day 1; lessthan 18 grams of protein for days 2 to 5 and any remaining days; 20-100or 20-30 grams of monounsaturated fats or more to reach the highercalorie intake for day 1; 6-30 or 6-10 grams of polyunsaturated fats ormore to reach the higher calorie intake for day 1; 2-12 grams ofsaturated fats or more to reach the higher calorie intake for day 1;10-50 or 10-15 grams of monounsaturated fats or more to reach the highercalorie intake for days 2 to 5 and any remaining days; 3-15 or 3-5 gramsof polyunsaturated fats or more to reach the higher calorie intake fordays 2 to 5 and any remaining days; 1-30 or 1-6 grams of saturated fatsor more to reach the higher calorie intake for days 2 to 5, or anyremaining days; and a micronutrient composition on each day and anyremaining days. In a refinement, the diet package also includesinstructions for administering the fasting mimicking diet in accordanceto the methods herein, and in particular, instructions for administeringthe diet package to a subject for treating autoimmune and/orinflammatory disease the instructions including the administrationschedule. To reach the higher calorie consumption described earlierwhich can be as high as a normal calorie intake, equal parts of the fatsdescribed above and of vegetable derived carbohydrate sources (vegetablesoups and chips) described elsewhere in the patent can be used. A FMDwith calories ranging from 50% restricted to normal, is expected to beeffective but less effective than the 50% or more restricted dietdescribed in this application.

In a variation, the fasting mimicking diet of the diet package provides8-25 or 8-10 kcal per kilogram body weight for each diet day; less than30 grams of sugar for each diet day; less than 18 grams of protein foreach diet day; and 9-30 or 9-15 grams of monounsaturated fats for eachdiet day, 2.5-9 or 2.5-4.5 grams of polyunsaturated fats for each dietday and 1-10 or 1-5.5 grams of saturated fats for each diet day. Inanother variation, the fasting mimicking diet of the diet packageprovides 5-8 kcal per kilogram body weight for each diet day; less than20 grams of sugar for each diet day; less than 12 grams of protein foreach diet day; and 6.5-10 grams of monounsaturated fats for each dietday, 2.5-4.5 grams of polyunsaturated fats for each diet day and 1.5-4grams of saturated fats for each diet day. In still another variation,the diet package provides 0-3 kcal per kilogram body weight for eachdiet day; less than 5 grams of sugar for each diet day; less than 3grams of protein for each diet day; and less than 2.5 grams ofmonounsaturated fats for each diet day, less than 1 grams ofpolyunsaturated fats for each diet day and less than 1 grams ofsaturated fats for each diet day.

The first set of rations can also provide 400-800 mg of calcium per dayfor days 1-5; 7.2-14.4 mg of iron per day for days 1-5; 200-400 mg ofmagnesium per day for days 1-5; 1-2 mg of copper per day for days 1-5;1-2 mg of manganese per day for days 1-5; and 3.5-7 mcg of selenium perday for days 1-5. In a refinement, the first set of rations provides 2-4mg of Vitamin B1 per day for days 1-5; 2-4 mg of Vitamin B2 per day fordays 1-5; 20-30 mg of Vitamin B3 per day for days 1-5; 1-1.5 mg ofVitamin B5 per day for days 1-5; 2-4 mg of Vitamin B6 per day for days1-5; 240-480 mcg of Vitamin B9 per day for days 1-5; 600-1000 IU ofVitamin D per day for days 1-5; 14-30 mg of Vitamin E per day for days1-5; over 80 mcg of Vitamin K per day for days 1-5; and 16-25 mcgVitamin B12 are provided during the predetermined time period. In afurther refinement, the first set of rations provides 600 mg ofDocosahexaenoic acid (DHA, algae-derived) during the predetermined timeperiod. In a refinement the first set of rations also provides acomponent having Vitamin A in an amount of 900-1600 IU; Ascorbic Acid inan amount of 10-20 mg; calcium carbonate in an amount of 60-100 mg;ferrous fumarate in an amount of 3-6 mg; cholecalciferol in an amount of0.001-0.005 mg; dl-alpha tocopheryl acetate in an amount 3-7 mg;phytonadione in an amount of 0.1-0.04 mg; thiamine mononitratein anamount of 0.15-0.5 mg; riboflavin in an amount 0.2-0.6 mg; andniacinamide in an amount of 3-7 mg. In a refinement the first set ofrations also provides a component having calcium pantothenate in anamount of 1.5-4.0 mg; pyridoxine hydrochloride in an amount of 0.3-0.7mg; biotin in an amount of 0.01-0.02 mg; folic acid in an amount of0.07-0.14 mg; cyanocobalamin in an amount of 0.001-0.002 mg; chromiumpicolinate in an amount of 0.014-0.022 mg; cupric sulfate in an amountof 0.18-0.32 mg; potassium iodide in an amount of 0.03-0.045 mg;magnesium oxide in an amount of 20-32 mg; manganese sulfate of 0.3-0.7mg; sodium molybdate in an amount of 0.014-0.023 mg; sodium selenate inan amount of 0.014-0.023 mg; and zinc oxide in an amount of 3-5 mg.

In some variations, the diet package includes a second set of rationsfor a second diet to be administered to the subject for a second timeperiod. The second diet providing an overall calorie consumption that iswithin 10 percent of a subject's normal calorie consumption for 25 to 26days following the first diet. In particular, the second diet providesthe caloric, food and nutritional specification for a subject's normaldiet as set forth above.

A particularly useful version of the fasting mimicking diet is disclosedin U.S. patent application Ser. No. 15/432,803 filed on Feb. 14, 2017;the entire disclosure of which is hereby incorporated by references. Inparticular, a diet package with certain specific meal components forimplementing a fasting mimicking diet in the method set forth herein isprovided. In a refinement, the diet package also includes instructionfor administering the fasting mimicking diet in accordance to themethods herein, and in particular, instructions for administering thediet package to a subject for treating autoimmune and/or inflammatorydisease with the instructions including the administration schedule. Inone variation, the fasting mimicking diet package and its associatedfasting mimicking diet provide daily meal portions for a predeterminednumber of days are set forth above (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or10 days). The fasting mimicking diet package includes a kale crackercomposition, a first vegetable broth composition, a mushroom soupcomposition, a tomato soup composition, a quinoa-containing minestronesoup composition, a bean-containing minestrone soup composition, and apumpkin soup composition. Characteristically, the daily meal portionsare packaged into meal servings or into a total daily serving to bedivided into meals. In a refinement, the fasting mimicking diet packageand its associated fasting mimicking diet further includes anut-containing nutrition bar, a cocoa-containing nutrition bar, a firstolive-containing composition, a first vegetable broth composition, a teacomposition that includes spearmint, a energy drink composition, amicronutritional composition, and an algal oil composition. In a furtherrefinement, the fasting mimicking diet package and its associatedfasting mimicking diet further includes a second olive-containingcomposition, a second vegetable broth composition, a tea compositionthat includes spearmint and lemon, and a tea composition that includeshibiscus. It should be appreciated that each of the soup, broth, tea andenergy compositions set forth herein are designed to have added waterwhen consumed.

In another variation of a fasting mimicking diet package, diet packageincludes a nut-containing nutrition bar, a cocoa-containing nutritionbar, a first olive-containing composition, a kale cracker composition, avegetable soup composition, a first vegetable broth composition, a teacomposition that includes spearmint, a energy drink composition, amicronutritional composition, and a algal oil composition.Characteristically, the daily meal portions are packaged into mealservings or into a total daily serving to be divided into meals. Thisdiet package also includes daily meal portions for a predeterminednumber of days as set forth above with the daily meal portions beingpackaged into meal servings or into a total daily serving to be dividedinto meals. In a refinement, the fasting mimicking diet package furtherincludes a mushroom soup composition, a tomato soup composition, aquinoa-containing minestrone soup composition, and a pumpkin soupcomposition. In a further refinement, the fasting mimicking diet packagefurther includes a second olive-containing composition, a secondvegetable broth composition, a bean-containing minestrone soupcomposition, a tea composition that includes spearmint and lemon, and atea composition that includes hibiscus.

As set forth above, the fasting mimicking diet packages includesspecific meal components that are administered for the fasting mimickingdiet. Typically, compositions are as follows. The nut-containingnutrition bar includes almond meal and macadamia nuts. Thecocoa-containing nutrition bar includes almond butter, almonds, andbrown rice crispy (e.g., brown puffed rice). The mushroom soupcomposition includes brown rice powder, carrots, inulin, and mushrooms.The bean-containing minestrone soup composition includes white beans,cabbage, and potatoes. The first vegetable broth composition includescarrots, maltodextrin, celery, spinach, and tomatoes. The secondvegetable broth composition includes carrots, maltodextrin, celery,spinach, soy lecithin, and tomatoes. The energy drink compositionincludes glycerin and water. The algal oil composition includesschizocatrium algae oil. The micronutrient composition includes beetroot powder, calcium carbonate, carrots, collard leaf, kale leaf, andtomatoes. In a refinement, the micronutrient composition includes Vit A,Vit C, Ca, Fe, Vit D3, Vit E, Vit K, Vit B1, Vit B2, Vit B3, Vit B5, VitB6, Vit B7, Vit B9, Vit B12, Cr, Cu, I, Mg, Mn, Mo, Se, and Zn.

In a refinement, the nut-containing nutrition bar (L-Bar Nut based)includes almond meal and macadamia nuts. In a refinement, thenut-containing nutrition bar (L-Bar Nut based) includes almond mealpreferably in an amount of 20 to 35 weight %; coconut preferably in anamount of 2 to 10 weight %; coconut oil preferably in an amount of 1 to8 weight %; flax seed meal preferably in an amount of 1 to 8 weight %;honey preferably in an amount of 10 to 30 weight %; macadamia nutspreferably in an amount of 10 to 30 weight %; pecans preferably in anamount of 10 to 25 weight %; salt preferably in an amount of 0.1 to 0.8weight %; and optionally vanilla preferably in an amount of 0.3 to 1.5weight %.

In a refinement, the cocoa-containing nutrition bar (L-Bar ChocoCrisp)includes almond butter, almonds, and brown rice crispy (PGP10235). In arefinement, the cocoa-containing nutrition bar (L-Bar ChocoCrisp)includes almond butter preferably in an amount of 10 to 25 weight %;almonds preferably in an amount of 3 to 12 weight %; brown rice crispy(PGP10235) preferably in an amount of 10 to 25 weight %; brown ricesyrup preferably in an amount of 2 to 8 weight %; chocolate liquorpreferably in an amount of 1 to 4 weight %, cocoa butter preferably inan amount of 0.4 to 1.6 weight %; cocoa powder preferably in an amountof 4 to 12 weight %; fiber syrup SF75 preferably in an amount of 18 to38 weight %, flax seed oil preferably in an amount of 1 to 3 weight %;salt preferably in an amount of 0.1 to 0.4 weight % and sugar preferablyin an amount of 1 to 6 weight %.

In a refinement, the first olive-containing composition (sea saltversion) includes olives, olive oil, and sea salt. In a refinement, thefirst olive-containing composition (sea salt) includes lactic acidpreferably in an amount of 0.3 to 1 weight %; oil (olive) preferably inan amount of 2 to 6 weight %; olives (raw, green pitted) preferably inan amount of 50 to 97 weight %; salt (reg., kosher, sea salt) preferablyin an amount of 0.8 to 3 weight %; and thyme preferably in an amount of0.1 to 0.5 weight %.

In a refinement, the second olive-containing composition (garlicversion) includes olives, olive oil, and garlic. In a refinement, thesecond olive-containing composition (garlic) includes garlic preferablyin an amount of 0.1 to 0.6 weight %; lactic acid preferably in an amountof 0.3 to 1 weight %; oil (olive) preferably in an amount of 2 to 6weight %; olives (raw, green pitted) preferably in an amount of 50 to 97weight %; salt (reg., kosher, sea salt) preferably in an amount of 0.8to 3 weight %; thyme preferably in an amount of 0.1 to 0.5 weight %.

In a refinement, the kale cracker composition includes kale, almonds,tapioca flour, and optionally sesame seeds. In another refinement, thekale cracker composition includes almonds preferably in an amount of 15to 40 weight %; black pepper preferably in an amount of 0.1 to 0.4weight %; chia seeds preferably in an amount of 3 to 10 weight %; chilipepper preferably in an amount of 0.4 to 1.2 weight %; cumin seedspreferably in an amount of 0.3 to 0.9 weight %; flax seeds preferably inan amount of 3 to 10 weight %; garlic preferably in an amount of 0.02 to0.04 weight %; kale preferably in an amount of 2 to 6 weight %; oil (sunflower) preferably in an about of 2 to 7 weight %; onion (powder,minced) typically in an amount of 0.3 to 0.9 weight %; oreganopreferably in an amount of 0.01 to 0.06 weight %; salt preferably in anamount of 1 to 4 weight %; sesame seeds preferably in an amount of 15 to35 weight %; sugar (coconut) preferably in an amount of 1 to 5 weight %;tapioca flour preferably in an amount of 10 to 30 weight %; vinegar(coconut) preferably in an amount of 1 to 4 weight %; water (purified)preferably in an amount of 2 to 12 weight %; and yeast extractpreferably in an amount of 0.3 to 1 weight %.

In another refinement, the kale cracker composition includes kale, flaxseeds golden, sesame seeds, and sunflower seeds. In another refinement,the apple cider vinegar preferably in an amount 1 to 3 weight %; blackpepper preferably in an amount of 0.4 to 1.3 weight %; cashewspreferably in an amount of 4 to 13 weight %; dill weed preferably in anamount of 0.4 to 1.3 weight %; flax seeds golden preferably in an amountof 13 to 40 weight %; hemp seeds preferably in an amount of 0.7 to 2weight %; kale preferably in an amount of 14 to 42 weight %; onion,white, dried, (powder, minced) preferably in an amount of 0.5 to 1.6weight %; pumpkin seeds preferably in an amount of 0.7 to 2 weight %;salt (reg., kosher, sea salt) preferably in an amount of 0.7 to 2 weight%; Sesame seeds preferably in an amount of 2 to 8 weight %; sunflowerseeds preferably in an amount of 10 to 30 weight %; and yeast extractpreferably in an amount of 1 to 5 weight %.

In a refinement, the vegetable soup composition includes onions,tomatoes, spinach, green tree extract, optionally rice flour, optionallybrown rice powder, optionally carrots, and optionally inulin, leeks, Ina refinement, the vegetable soup composition includes basil (whole leaf,dried) preferably in an amount of 0.3 to 0.9 weight %; brown rice powder(whole grain) preferably in an amount of 3 to 12 weight %; carrot(dehydrated, puffed, powder, pieces) preferably in an amount of 4 to 14weight %; green tea extract preferably in an amount of 0.02 to 0.06weight %; inulin preferably in an amount of 5 to 15 weight %; leeks(granules—10+40) preferably in an amount of 1 to 5 weight %; oil (olive)preferably in an amount of 1 to 6 weight %; onion (powder, minced)preferably in an amount of 4 to 15 weight %; parsley preferably in anamount of 0.3 to 0.8 weight %; red bell peppers preferably in an amountof 1 to 5 weight %; rice flour preferably in an amount of 18 to 50weight %; salt preferably in an amount of 2 to 7 weight %; spinach(leaf, powder) preferably in an amount of 0.4 to 1.5 weight %; tomatoes(fruit powder, sun dried, granules) preferably in an amount of 4 to 14weight %; yeast extract preferably in an amount of 0.5 to 1.8 weight %.In the vegetable soup composition and any of the compositions set forthherein having rice flour, the rice flour can be glutinous ornon-glutinous, milled or unmilled.

In another refinement, the vegetable soup composition includes carrots,inulin, leeks, onions and rice flour. In a refinement, the vegetablesoup composition includes basil, whole leaf, dried preferably in anamount of 0.3 to 1 weight %; carrot (dehydrated, puffed, powder, pieces)preferably in an amount of 4 to 12 weight %; inulin preferably in anamount of 6 to 18 weight %; leeks in an amount of 1 to 5 weight %; oil(olive) preferably in an amount of 1 to 3 weight %; Onion, white, dried,(powder, minced) preferably in an amount of 10 to 30 weight %; parsleypreferably in an amount of 0.3 to 1 weight %; potato preferably in anamount of 1 to 5 weight %; red pepper preferably in an amount of 1 to 6weight %; rice flour in an amount of 13 to 40 weight %; salt (reg.,kosher, sea salt) in an amount of 4 to 12 weight %; spinach (leaf,powder) preferably in an amount of 0.2 to 1 weight %; and tomatoes,(fruit powder, sun dried granules) preferably in an amount of 3 to 13weight %.

In a refinement, the mushroom soup composition includes mushrooms, greentea extract, optionally brown rice powder, optionally carrots, andoptionally inulin. In a refinement, the mushroom soup compositionincludes brown rice powder (whole grain) preferably in an amount of 10to 30 weight %; carrot (dehydrated, puffed, powder, pieces) preferablyin an amount of 3 to 12 weight %; green tea extract preferably in anamount of 0.02 to 0.06 weight %; inulin preferably in an amount of 3 to12 weight %; mushrooms (European mix, powder, pieces) preferably in anamount of 6 to 18 weight %; oil (olive) preferably in an amount of 1 to6 weight %; onion preferably in an amount of powder, minced) preferablyin an amount of 3 to 12 weight %; parsley preferably in an amount of 0.1to 0.5 weight %; rice flour preferably in an amount of 18 to 50 weight%; salt preferably in an amount of 2 to 8 weight %; yeast extractpreferably in an amount of 0.5 to 1.5 weight %.

In another refinement, the mushroom soup composition includes carrots,inulin, mushrooms, onions, and rice flour. In another refinement, themushroom soup composition includes carrot (dehydrated, puffed, powder,pieces) preferably in an amount of 7 to 22 weight %; inulin preferablyin an amount of 7 to 22 weight %; mushrooms (European mix), (powder &pieces) dehydrated preferably in an amount of 7 to 22 weight %; oil(olive) preferably in an amount of 0.6 to 2 weight %; Onion, white,dried, (powder, minced) preferably in an amount of 7 to 22 weight %;parsley preferably in an amount of 0.3 to 0.9 weight %; potatopreferably in an amount of 0.6 to 2 weight %; rice flour preferably inan amount of 15 to 45 weight %; salt (reg., kosher, sea salt) preferablyin an amount of 6 to 18 weight %; and yeast extract preferably in anamount of 0.7 to 2.2 weight %.

In a refinement, the tomato soup composition includes tomatoes, greentea extract, optionally inulin, and optionally onions. In a refinement,the tomato soup composition (new) includes basil (whole leaf, dried)preferably in an amount of 0.2 to 0.7 weight %; brown rice powder (wholegrain) preferably in an amount of 1 to 5 weight %; green tea extractpreferably in an amount of 0.02 to 0.06 weight %; inulin preferably inan amount of 7 to 20 weight %; oil (olive) preferably in an amount of 3to 9 weight %; onion preferably (powder, minced) preferably in an amountof 4 to 12 weight %; parsley preferably in an amount of 0.1 to 0.6weight %; rice flour preferably in an amount of 18 to 50 weight %; saltpreferably in an amount of 2 to 9 weight %; tomatoes (fruit powder, sundried, granules) preferably in an amount of 12 to 36 weight %; and yeastextract preferably in an amount of 0.5 to 3 weight %.

In another refinement, the tomato soup composition includes tomatoes,inulin, olives, onions, potatoes, and rice flour. In still anotherrefinement, the tomato soup composition includes basil, whole leaf,dried preferably in an amount of 0.3 to 1 weight %; inulin preferably inan amount of 6 to 18 weight %; oil (olive) preferably in an amount of 4to 14 weight %; onion, white, dried, (powder, minced) preferably in anamount of 8 to 24 weight %; parsley preferably in an amount of 0.3 to0.9 weight %; potato preferably in an amount of 6 to 18 weight %; riceflour preferably in an amount of 9 to 27 weight %; salt (reg., kosher,sea salt) preferably in an amount of 4 to 14 weight %; tomatoes, (fruitpowder, sun dried granules) preferably in an amount of 8 to 24 weight %;and yeast extract preferably in an amount of 0.7 to 2.2 weight %.

In a refinement, the quinoa-containing minestrone soup compositionincludes quinoa, green tea extract, optionally olive oil, optionallycabbage, optionally potatoes, optionally rice flour, and optionallytomatoes and optionally no tumeric. In a refinement, thequinoa-containing minestrone soup composition includes basil (wholeleaf, dried preferably in an amount of 0.7 to 2 weight %; broccolipowder preferably in an amount of 0.6 to 2 weight %; cabbage white(flakes) preferably in an amount of 3 to 10 weight %; carrot(dehydrated, puffed, powder, pieces) preferably in an amount of 3 to 10weight %; celery preferably in an amount of 1 to 4 weight %; celeryseeds (powder) preferably in an amount of 0.07 to 0.2 weight %; garlicpreferably in an amount of 0.7 to 2 weight %; green tea extractpreferably in an amount of 0.02 to 0.06 weight %; inulin preferably inan amount of 1 to 5 weight %; leeks (granules—10+40), preferably in anamount of 0.7 to 2 weight %; oil (olive) preferably in an amount of 0.6to 2 weight %; onion (powder, minced) preferably in an amount of 2 to 8weight %; peas preferably in an amount of 3 to 10 weight %; potatopreferably in an amount of 7 to 20 weight %; quinoa preferably in anamount of 7 to 20 weight %; rice flour preferably in an amount of 7 to20 weight %; salt, preferably in an amount of 1 to 6 weight %; spinach(leaf, powder) preferably in an amount of 0.5 to 2 weight %; tomatoes(fruit powder, sun dried, granules) preferably in an amount of 2 to 6weight %; yeast extract preferably in an amount of 0.6 to 2 weight %;zucchini (powder, diced) preferably in an amount of 2 to 8 weight %.

In another refinement, the quinoa-containing minestrone soup includesquinoa, cabbage, potatoes, and rice flour. In still another refinement,the quinoa-containing minestrone soup includes basil, whole leaf, driedpreferably in an amount of 0.7 to 2.2 weight %; broccoli powderpreferably in an amount of 0.7 to 2.2 weight %; cabbage white (flakes)preferably in an amount of 0.6 to 2.2 weight %; carrot (dehydrated,puffed, powder, pieces) preferably in an amount of 3 to 10 weight %;celeriac preferably in an amount of 2 to 6 weight %; celery seeds powderpreferably in an amount of 0.6 to 1.8 weight %; garlic preferably in anamount of 1 to 3 weight %; Onion, white, dried, (powder, minced)preferably in an amount of 3 to 9 weight %; peas preferably in an amountof 3 to 10 weight %; potato preferably in an amount of 6 to 20 weight %;quinoa preferably in an amount of 8 to 23 weight %; rice flourpreferably in an amount of 7 to 22 weight %; salt (reg., kosher, seasalt) preferably in an amount of 2 to 7 weight %; savoy cabbagepreferably in an amount of 3 to 10 weight %; spinach (leaf, powder)preferably in an amount of 0.7 to 2.2 weight %; turmeric preferably inan amount of 0.6 to 1.8 weight %; yeast extract preferably in an amountof 3 to 10 weight %; and zucchini (powder, diced) preferably in anamount of 1 to 5 weight %.

In a refinement, the bean-containing minestrone soup compositionincludes white beans (e.g., great northern beans), great tea extract,optionally cabbage, and optionally potatoes. In a refinement, thebean-containing minestrone soup composition includes beans (greatnorthern) preferably in an amount of 3 to 10 weight %; cabbage white(flakes) preferably in an amount of 2 to 8 weight %; carrot (dehydrated,puffed, powder, pieces) preferably in an amount of 2 to 8 weight %;celery preferably in an amount of 1 to 4 weight %; green tea extractpreferably in an amount of 0.02 to 0.06 weight %; inulin preferably inan amount of 2 to 10 weight %; leeks (granules—10+40) preferably in anamount of 2 to 7 weight %; oil (olive) preferably in an amount of 2 to 7weight %; onion (powder, minced) preferably in an amount of 2 to 7weight %; parsley preferably in an amount of 0.2 to 1 weight %; peaspreferably in an amount of 3 to 9 weight %; potato preferably in anamount of 15 to 45 weight %; rice flour preferably in an amount of 6 to18 weight %; salt preferably in an amount of 2 to 8 weight %; spinach(leaf, powder) preferably in an amount of 0.5 to 1.5 weight %; tomatoes(fruit powder, sun dried, granules) preferably in an amount of 2 to 7weight %; and yeast extract preferably in an amount of 0.5 to 1.5 weight%.

In a refinement, the bean-containing minestrone soup compositionincludes brown beans, carrots, peas, potato, and rice flour. In anotherrefinement, the bean-containing minestrone soup composition includescarrot (dehydrated, puffed, powder, pieces) preferably in an amount of 4to 14 weight %; celeriac preferably in an amount of 1 to 5 weight %;celery preferably in an amount of 0.5 to 1.6 weight %; leeks preferablyin an amount of 2 to 8 weight %; oil (olive) preferably in an amount of2 to 8 weight %; Onion, white, dried, (powder, minced) preferably in anamount of 3 to 10 weight %; parsley preferably in an amount of 0.5 to1.5 weight %; peas preferably in an amount of 5 to 18 weight %; potatopreferably in an amount of 8 to 24 weight %; rice flour preferably in anamount of 5 to 18 weight %; salt (reg., kosher, sea salt) preferably inan amount of 4 to 14 weight %; spinach (leaf, powder) preferably in anamount of 0.5 to 1.5 weight %; tomatoes, (fruit powder, sun driedgranules) preferably in an amount of 0.9 to 2.8 weight %; turmericpreferably in an amount of 0.3 to 1.2 weight %; and yeast extractpreferably in an amount of 0.5 to 1.5 weight %.

In a refinement, the pumpkin soup composition includes pumpkin, greentree extract, optionally rice flour, optionally carrots, and optionallybrown rice powder. In a refinement, the pumpkin soup compositionincludes (new) includes brown rice powder (whole grain) preferably in anamount of 3 to 9 weight %; carrot (dehydrated, puffed, powder, pieces)preferably in an amount of 2 to 8 weight %; green tea extract preferablyin an amount of 0.02 to 0.06 weight %; inulin preferably in an amount of2 to 10 weight %; oil (olive) preferably in an amount of 1 to 7 weight%; onion (powder, minced) preferably in an amount of 1.0 to 3 weight %;pumpkin powder preferably in an amount of 20 to 60 weight %; rice flourpreferably in an amount of 15 to 45 weight %; salt preferably in anamount of 2 to 10 weight %; and yeast extract preferably in an amount of0.3 to 1 weight %.

In a refinement, the first vegetable broth includes carrots,maltodextrin, celery, spinach, and tomatoes. In a refinement, the firstvegetable broth includes carrot (dehydrated, puffed, powder, pieces)preferably in an amount of 6 to 18 weight %; celery preferably in anamount of 3 to 10 weight %; garlic preferably in an amount of 3 to 10weight %; maltodextrin preferably in an amount of 8 to 25 weight %; oil(canola) preferably in an amount of 0.5 to 2 weight %; onion (powder,minced) preferably in an amount of 6 to 18 weight %; parsley preferablyin an amount of 3 to 10 weight %; potato preferably in an amount of 1 to3 weight %; salt preferably in an amount of 7 to 21 weight %; spinach(leaf, powder) preferably in an amount of 3 to 10 weight %; tomatoes(fruit powder, sun dried, granules) preferably in an amount of 6 to 18weight %; and yeast extract preferably in an amount of 1 to 6 weight %.

In a refinement, the second vegetable broth (chicken flavoring) includescarrots, chicken flavoring, maltodextrin, celery, spinach, soy lecithin,and tomatoes. In a refinement, the second vegetable broth compositionincludes carrot (dehydrated, puffed, powder, pieces) preferably in anamount of 3 to 10 weight %; celery preferably in an amount of 3 to 12weight %; garlic preferably in an amount of 3 to 9 weight %;maltodextrin preferably in an amount of 8 to 25 weight %; oil (canola)preferably in an amount of 0.5 to 2 weight %; onion preferably in anamount of powder, minced) preferably in an amount of 3 to 12 weight %;parsley preferably in an amount of 3 to 10 weight %; potato preferablyin an amount of 1 to 6 weight %; salt preferably in an amount of 8 to 25weight %; soy lecithin preferably in an amount of 0.5 to 3 weight %;spinach (leaf, powder) preferably in an amount of 3 to 12 weight %;tomatoes (fruit powder, sun dried, granules) preferably in an amount of6 to 18 weight %; xanthan gum preferably in an amount of 0.5 to 4 weight%; and yeast extract preferably in an amount of 4 to 12 weight %.

In a refinement, the energy drink composition includes glycerinpreferably in an amount of 20 to 60 weight %; water (purified)preferably in an amount of 40 to 80 weight %.

In a refinement, the tea composition that includes spearmint includesspearmint leaves organic preferably in an amount of 70 to 100 weight %.

In a refinement, the tea composition that includes lemon and spearmintincludes lemon myrtle organic preferably in an amount of 3 to 12 weight%; lemon peel organic preferably in an amount of 10 to 25 weight %;spearmint leaves organic preferably in an amount of 50 to 95 weight %.

In a refinement, the tea composition that includes hibiscus includeshibiscus tea leaves organic preferably in an amount of 80 to 100 weight%.

In a refinement, the algal oil composition includes schizocatrium algaeoil (DHA Omega-3) preferably in an amount of 80 to 100 weight %.

In a refinement, the nutrient replenishment composition (NR-1) includesbeet root powder, calcium carbonate, carrots, collard leaf, kale leaf,and tomatoes. In a refinement, the nutrient replenishment composition(NR-1) includes ascorbic acid preferably in an amount of 1 to 3 weight%; beet root powder preferably in an amount of 6 to 20 weight %; betacarotene preferably in an amount of 0.05 to 0.15 weight %; calciumcarbonate preferably in an amount of 6 to 20 weight %; carrot(dehydrated, puffed, powder, pieces) preferably in an amount of 6 to 20weight %; cholecaliciferol preferably in an amount of 0.00 weight %;chromium Picolinate preferably in an amount of 0.00 weight %; collardleaf powder preferably in an amount of 6 to 20 weight %; cupric sulfatepreferably in an amount of 0.01 to 0.06 weight %; cyanocobalamin, 0.00;Dl-alpha tocopherol acetate preferably in an amount of 0.3 to 1 weight%; ferrous fumarate preferably in an amount of 0.2 to 1 weight %; folicacid preferably in an amount of 0.00 weight %; kale leaf preferably inan amount of 6 to 20 weight %; magnesium stearate preferably in anamount of 1 to 6 weight %; manganese sulfate preferably in an amount of0.04 to 0.08 weight %; niacinamide preferably in an amount of 0.3 to 1weight %; pantothenic acid preferably in an amount of 0.1 to 0.6 weight%; phytonadione preferably in an amount of 0.00 weight %; potassiumiodine preferably in an amount of 0 weight %; pyriodoxine HCl preferablyin an amount of 0.03 to 0.1 weight %; riboflavin preferably in an amountof 0.02 to 0.1 weight %; sodium molybdate preferably in an amount of0.00 weight %; sodium selenate preferably in an amount of 0.00 weight %;spinach (leaf, powder) preferably in an amount of 6 to 20 weight %;thiamine mononitrate preferably in an amount of 0.02 to 0.1 weight %;tomatoes (fruit powder, sun dried, granules) preferably in an amount of6 to 20 weight %; tribasic calcium phosphate preferably in an amount of0.5 to 2 weight %; and zinc oxide preferably in an amount of 0.2 to 0.8weight %.

In a variation, the each of the components of the fasting mimicking dietpackage and therefore the fasting mimicking diet, is substantiallygluten free (e.g., each component has less than 20 ppm gluten) or verylow gluten (e.g., each component has 20-100 ppm). In other variations,each of the components are provided in a serving size from 20 to 60 g.In other variations, the nut-containing nutrition bar is provided in aserving size from 30 to 60 g; cocoa-containing nutrition bar is providedin a serving size from 15 to 40 g; the olive containing composition (seasalt version) in a serving size from 10 to 20 g; the olive containingcomposition (garlic version) in a serving size from 10 to 20 g; kalecracker composition is provides in a serving size from 30 to 60 g; Inanother variation, the kale cracker compositions are provided in aserving size from 20 to 50 g; the vegetable soup compositions areprovided in a serving size from 20 to 50 g; the mushroom soupcompositions are provided in a serving size from 20 to 50 g; the tomatosoup compositions are provided in a serving size from 20 to 50 g; thebean-containing minestrone soup compositions are provided in a servingsize from 20 to 50 g; the quinoa-containing minestrone soup compositionsare provided in a serving size from 20 to 50 g; the pumpkin soupcompositions are provided in a serving size from 20 to 50; the firstvegetable both compositions are provided in a serving size from 5 to 15;the second vegetable both compositions are provided in a serving sizefrom 3 to 15; and Energy Drink composition is provided in serving sizeof 1 to 5 oz.

The following examples illustrate the various embodiments of the presentinvention. Those skilled in the art will recognize many variations thatare within the spirit of the present invention and scope of the claims.

Here we show that the fasting mimicking diet (FMD) as an intensive butbrief form of a dietary intervention that can alter the numerical andfunctional profiles of innate and adaptive immunity and levels ofcirculating cytokines which are key therapeutic targets of majority ofautoimmune (Table 1) in addition to promoting intestinal regeneration.

We show that cycles of FMD can alleviate the gastrointestinalautoimmune/inflammatory family of diseases called inflammatory boweldisease (IBD, Crohn's disease and ulcerative colitis; FIG. 1 and Table2) by reducing the number of circulating innate immunity (macrophagesand dendritic cells; Table 4), and T lymphocytes (Th1 and Th17; Table 5)while increasing anti-inflammatory CD4⁺ T regulatory cells (Treg; Table5). FMD cycles reduces pro-inflammatory cytokines related to autoimmunedisease (IFN-γ and IL-17; Table 6) while increasing anti-inflammatorycytokine (IL-10; Table 6). Furthermore, FMD induces production ofendogenous glucocorticoid levels (FIG. 2 ), which are known to play animportant role as anti-inflammatory and immunosuppressive effects¹⁷⁻²⁰.This high efficiency, broad effects on both innate and adaptive immuneresponse with minimal initial requirements and long-term safety/benefitsallow this invention to incorporate into various types of therapy,including biological and pharmaceutical therapies. We also show that thecycles of FMD promote the growth of the intestine after it is shortenedupon IBD induction (Table 3). The regenerative effects of the FMD cycleson various stem cells in both mice and humans of pancreatic,hematopoietic, liver, and neural cells, indicate that FMD cycles canpromote intestinal regeneration. Overall, the FMD cycles poses a greatpotential in both preventive and treatments for gastrointestinalautoimmune/inflammatory diseases, demonstrated here in inflammatorybowel disease model that includes both Crohn's disease and ulcerativecolitis. With no need for invasive approach, it can benefit theconventional immunoregulatory approach in the way that directlyregulates the dendritic cells, macrophages, and B-T lymphocytepopulations and/or may indirectly change the cytokines or hormones toameliorate the inflammatory autoimmune insults. Compared to establishedtherapies against IBDs, this represents the first therapy that 1) causesa coordinated reduction in inflammation/autoimmunity which return to thenormal immune cell levels after re-feeding, and 2) causes regenerationand healing of the damaged tissue.

As 120-hr fasting is extremely difficult for human subjects to achievedue to the low compliance and the side-effects of malnutrition. Thepresent invention makes use of a previously identified FMD tested inboth animal studies and clinical trials (U.S. patent application Ser.No. 14/178,953) which maximize the micronutrient contents, whileproviding a sufficient level of calories without interfering with theeffects of fasting on the modulation of the immune and gastrointestinalsystems.

Cycles of a FMD reduced dendritic cell, macrophages, B-lymphocytes,CD4+Th1 and CD4+Th17 cell populations while increase anti-inflammatoryregulatory T cells. Furthermore, FMD treatment reduces pro-inflammatorycytokines (IFN-γ and IL-17) while it increases anti-inflammatorycytokine (IL-10) and hormone (glucocorticoid). FMD cycles causedregeneration in the intestine damaged by the IBD. FMD treatmentsalleviated the symptoms in the mouse models of inflammatory boweldisease.

The experimental mouse FMD is based on a nutritional screen thatidentified ingredients which allow high nourishment during periods oflow calorie consumption²¹. The FMD diet consists of two differentcomponents designated as day 1 diet and day 2-3 diet that were fed inthis order respectively. Day 1 diet contains 7.87 kJ/g, the day 2-3 dietis identical on all feeding days and contains 1.51 kJ/g. Day 1 and day2-3 diets were supplied to the FMD cohort with the average intake of thead lib control group (˜4 g) every two weeks. On average, mice consumed11.07 kJ (plant-based protein 0.75 kJ, carbohydrate 5.32 kJ, fat 5 kJ)on each day of the FMD regimen. Mice consumed all the supplied food oneach day of the FMD regimen and showed no signs of food aversion.

We supplied TD.7912 chow ad lib for 4 to 7 days after the end of the day2-3 diet. The duration of FMD and that of refeeding with TD.7912 may beadjusted by the body weight loss (≤20%) and recovery (≥95%). Prior tosupplying the FMD diet, animals were transferred into fresh cages toavoid feeding on residual chow and coprophagy.

The modified human FMD will substitute a subjects' normal diet for aperiod of 5 days:

Diet 1: the FMD will substitute a subject's normal diet for a period of5 days every 2-12 weeks depending on the need of the subject in terms ofbody weight and disease risk factor management. For day 1, the FMD willprovide 4.5-7 kcal per pound of body weight (or 10-16 kcal per kilogrambody weight). For days 2-5, the FMD will provide 3-5 kcal per pound ofbody weight (or 7-11 kcal per kilogram body weight). The day 1 dietshould contain less than 30 grams of sugar, less than 28 grams ofprotein, 20-30 grams of monounsaturated fats, 6-10 grams ofpolyunsaturated fats and 2-12 grams of saturated fats. The Day 2-5 dietsshould contain less than 20 grams of sugar, less than 18 grams ofprotein, 10-15 grams of monounsaturated fats, 3-5 grams ofpolyunsaturated fats and 1-6 grams of saturated fats. The diet will alsoprovide micronutrients at greater than 25% of the Daily Value (DV). Inan alternative method the diet can be administered for only 1 day with afrequency of at least 1 day/week every week of the month.

Diet 2: Diet 2: the FMD will substitute a subject's normal diet for aperiod of 2 days every week. The FMD will provide 3-5 kcal per pound ofbody weight (or 7-11 kcal per kilogram body weight). The day 1 dietshould contain less than 30 grams of sugar, less than 28 grams ofprotein, 20-30 grams of monounsaturated fats, 6-10 grams ofpolyunsaturated fats and 2-12 grams of saturated fats. The day 2 dietshould contain less than 20 grams of sugar, less than 18 grams ofprotein, 10-15 grams of monounsaturated fats, 3-5 grams ofpolyunsaturated fats and 1-6 grams of saturated fats. The diet will alsoprovide micronutrients at greater than 25% of the Daily Value (DV).

While exemplary embodiments are described above, it is not intended thatthese embodiments describe all possible forms of the invention. Rather,the words used in the specification are words of description rather thanlimitation, and it is understood that various changes may be madewithout departing from the spirit and scope of the invention.Additionally, the features of various implementing embodiments may becombined to form further embodiments of the invention.

REFERENCES

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What is claimed is:
 1. A method for treating autoimmune and/orinflammatory disease, the method comprising: a) administering a fastingmimicking diet (FMD) for a first time period to a subject havingulcerative colitis, the first time period being 1, 2, 3, 4, 5, 6, 7, 8,9, or 10 days, wherein the fasting mimicking diet provides from 4.5 to 7kilocalories per pound of subject for a first day of the fastingmimicking diet, wherein on day 1, the fasting mimicking diet providesless than 30 grams of sugar, less than 28 grams of protein, 20-30 gramsof monounsaturated fats, 6-10 grams of polyunsaturated fats and 2-12grams of saturated fats and on days 2-5 the fasting mimicking dietprovides less than 20 grams of sugar, less than 18 grams of protein,10-15 grams of monounsaturated fats, 3-5 grams of polyunsaturated fatsand 1-6 grams of saturated fats.
 2. The method of claim 1 wherein thehypocaloric or calorie free diet or fasting mimicking diet isadministered for a period of 5 days every 2-12 weeks.
 3. The method ofclaim 1 wherein step a) is repeated a plurality of times atpredetermined intervals.
 4. The method of claim 3 wherein step a) isrepeated at intervals from one week to 6 months.
 5. The method of claim3 wherein the subject is administered a normal diet in betweenrepetition of step a).
 6. The method of claim 1 wherein the FMD provides3-5 kilocalories per pound of subject per day for a second day to thefinal day of the fasting mimicking diet.
 7. The method of claim 1wherein the FMD also provides vitamin A in an amount of 900-1600 IU;ascorbic acid in an amount of 10-20 mg; calcium carbonate in an amountof 60-100 mg; ferrous fumarate in an amount of 3-6 mg; cholecalciferolin an amount of 0.001-0.005 mg; dl-alpha tocopheryl acetate in an amount3-7 mg; phytonadione in an amount of 0.1-0.04 mg; thiamine mononitrateinan amount of 0.15-0.5 mg; riboflavin in an amount 0.2-0.6 mg; andniacinamide in an amount of 3-7 mg.
 8. The method of claim 1 wherein theFMD is administered for only 1 day with a frequency of at least 1day/week every week of a month.
 9. The method of claim 1 wherein the FMDwill substitute a subject's normal diet for a period of 2 days everyweek.
 10. The method of claim 1 wherein a day 1 FMD diet contains lessthan 30 grams of sugar, less than 28 grams of protein, 20-30 grams ofmonounsaturated fats, 6-10 grams of polyunsaturated fats and 2-12 gramsof saturated fats.
 11. The method of claim 10 wherein a day 2 FMD dietincludes less than 20 grams of sugar, less than 18 grams of protein,10-15 grams of monounsaturated fats, 3-5 grams of polyunsaturated fatsand 1-6 grams of saturated fats.
 12. The method of claim 11 wherein theFMD also provides vitamin A in an amount of 900-1600 IU; ascorbic acidin an amount of 10-20 mg; calcium carbonate in an amount of 60-100 mg;ferrous fumarate in an amount of 3-6 mg; cholecalciferol in an amount of0.001-0.005 mg; dl-alpha tocopheryl acetate in an amount 3-7 mg;phytonadione in an amount of 0.1-0.04 mg; thiamine mononitratein anamount of 0.15-0.5 mg; riboflavin in an amount 0.2-0.6 mg; andniacinamide in an amount of 3-7 mg.
 13. The method of claim 1 whereinthe fasting mimicking diet is administered as a first set of rationsproviding: less than 40 grams of sugar for day 1; less than 30 grams ofsugar for days 2 to 5 and any remaining days; less than 28 grams ofprotein for day 1; less than 18 grams of protein for days 2 to 5 and anyremaining days; 20-100 grams of monounsaturated fats for day 1; 6-30grams of polyunsaturated fats for day 1; 2-12 grams of saturated fatsfor day 1; 10-50 grams of monounsaturated fats for days 2 to 5 and anyremaining days; 3-15 grams of polyunsaturated fats for days 2 to 5 andany remaining days; 1-12 grams of saturated fats for days 2 to 5, or anyremaining days; and a micronutrient composition on each day and anyremaining days.
 14. The method of claim 13 wherein the fasting mimickingdiet provides: 8-10 kcal per kilogram body weight for each diet day:less than 30 grams of sugar for each diet day; less than 18 grams ofprotein for each diet day; and 9-15 grams of monounsaturated fats foreach diet day, 2.5-4.5 grams of polyunsaturated fats for each diet dayand 1-5.5 grams of saturated fats for each diet day.
 15. The method ofclaim 13 wherein the fasting mimicking diet provides: less than 20 gramsof sugar for each diet day; less than 12 grams of protein for each dietday; and 6.5-10 grams of monounsaturated fats for each diet day, 2.5-4.5grams of polyunsaturated fats for each diet day and 1.5-4 grams ofsaturated fats for each diet day.
 16. The method of claim 13 wherein thefasting mimicking diet includes Vitamin A in an amount of 900-1600 IU;Ascorbic Acid in an amount of 10-20 mg; calcium carbonate in an amountof 60-100 mg; ferrous fumarate in an amount of 3-6 mg; cholecalciferolin an amount of 0.001-0.005 mg; dl-alpha tocopheryl acetate in an amount3-7 mg; phytonadione in an amount of 0.1-0.04 mg; thiamine mononitratein an amount of 0.15-0.5 mg; riboflavin in an amount 0.2-0.6 mg; andniacinamide in an amount of 3-7 mg.
 17. The method of claim 16 whereinthe fasting mimicking diet includes calcium pantothenate in an amount of1.5-4.0 mg; pyridoxine hydrochloride in an amount of 0.3-0.7 mg; biotinin an amount of 0.01-0.02 mg; folic acid in an amount of 0.07-0.14 mg;cyanocobalamin in an amount of 0.001-0.002 mg; chromium picolinate in anamount of 0.014-0.022 mg; cupric sulfate in an amount of 0.18-0.32 mg;potassium iodide in an amount of 0.03-0.045 mg; magnesium oxide in anamount of 20-32 mg; manganese sulfate of 0.3-0.7 mg; sodium molybdate inan amount of 0.014-0.023 mg; sodium selenate in an amount of 0.014-0.023mg; and zinc oxide in an amount of 3-5 mg.
 18. The method of claim 13further comprising a second set of rations for a second diet to beadministered to the subject for a second time period, the second dietproviding an overall calorie consumption that is within 10 percent of asubject's normal calorie consumption for 25 to 26 days following thefasting mimicking diet.
 19. The method of claim 1 wherein the fastingmimicking diet is administered in a sufficient number of cycles toreduce dendritic cells, macrophages, B-lymphocytes, CD4+Th1, andCD4+Th17 cell populations and to increase anti-inflammatory regulatory Tcells.